A complement system plays a first step in innate immunity to most rapidly recognize and destroy an infection source. In addition, the complement system plays an important role in bridging between innate immunity and adaptive immunity by interaction with immune cells. The complement system is activated by a classical pathway, an alternative pathway and a lectin pathway, and then various kinds of complement proteins are activated. The complement proteins activate secretion of inflammatory substances, control an inflammatory response by interaction with immune cells, and effectively eliminate external infection sources by creating materials attacking the infection source, and the like. It is known that since the complement system inhibits an excessive increase in complementary activity by various kinds of complement regulatory proteins, maintains homeostasis, and plays a critical role through various steps of an inflammatory response and an immune response, when complement protein and complement regulatory protein are not properly controlled, various diseases are caused.
When the complement system is activated by the classical pathway, the alternative pathway and the lectin pathway, Complement component 5 (C5) convertase cleaves C5 into C5a and C5b.
C5 is expressed intracellularly as a single pro-C5 peptide of 1676 amino acids consisting of 18 residue signal sequences and an Arg-rich linker sequence (RPRR) between a mature N-terminal β-chain and a C-terminal α-chain. The mature C5 has a molecular weight of about 190 kDa, and consists of two polypeptide chains (α, 115 kDa and β, 75 kDa) which are connected by disulfide bonds. The C5 convertase cleaves C5 between residues 74 and 75 of the alpha chain to release the 74 amino acid C5a peptide and the C5b fragment which are subsequently incorporated into the membrane-attack complex (MAC).
C5a which is anaphylatoxin, directly activates white blood cells and platelets, and functions as a chemotactic factor of a neutrophil. C5b forms a membrane attack complex together with C6, C7, C8 and C9 in a final step of complement activation to induce hemolysis.
When the complement system is over-activated, since abnormal immune response, and damage of normal cells occur, abnormal activity of the complement system is related with autoimmune diseases, complement-related diseases, and the like. A hemolytic blood disease is a complement-related disease occurring when blood cells are not protected from attack of complement proteins due to genetic defects. It has been reported that complement activation is also related with vigorous immune response and tissue destruction reaction that occur in rheumatoid arthritis, transplant, and the like, and materials such as VEGF are released by tissue damage as well as the immune reaction by the complement activation to cause angiogenesis, which leads to elderly-related macular degeneration and diabetic retinopathy.
That is, the complement system plays an important role in maintaining health; however, it potentially causes diseases or contributes to occurrence of diseases. Accordingly, it is preferable to develop a novel antibody, and the like, of a complement system to be used for treating and diagnosing complement-related diseases.
There are provided a composition comprising a complement inhibitor, a method for treating or preventing complement-related diseases, and a use thereof.